CALCRL

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CALCRL
3N7S.pdb.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CALCRL, CGRPR, CRLR, calcitonin receptor like receptor
External IDs MGI: 1926944 HomoloGene: 21179 GeneCards: CALCRL
RNA expression pattern
PBB GE CALCRL 206331 at fs.png

PBB GE CALCRL 210815 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001271751
NM_005795

NM_018782

RefSeq (protein)

NP_001258680
NP_005786

NP_061252.2
NP_061252

Location (UCSC) Chr 2: 187.34 – 187.45 Mb Chr 2: 84.33 – 84.43 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Calcitonin receptor-like (CALCRL), also known as the calcitonin receptor-like receptor (CRLR), is a human protein.[3]

Function[edit]

The protein encoded by the CALCRL gene is a G protein-coupled receptor related to the calcitonin receptor. CALCRL is linked to one of three single transmembrane domain receptor activity-modifying proteins (RAMPs) that are essential for functional activity.

The association of CALCRL with different RAMP proteins produces different receptors:[4][5]

These receptors are linked to the G protein Gs,[7] which activates adenylate cyclase and activation results in the generation of intracellular cyclic adenosine monophosphate (cAMP).

Structure[edit]

CALCRL associated with RAMP 1 produces the CGRP receptor which is a trans-membrane protein receptor that is made up of four chains. Two of the four chains contain unique sequences. It is a heterodimer protein composed of two polypeptide chains differing in composition of their amino acid residues. The sequence reveals multiple hydrophobic and hydrophilic regions throughout the four chains in the protein.[8]

The structural dynamics of an active state complex of the Calcitonin receptor-like protein, CGRP, the Receptor Activity-Modifying Protein 1, and the G-protein C-terminus has been elucidated using a computational and experimental approach.[9]

Clinical significance[edit]

These G-protein coupled receptor (GPCRs) proteins play an important role in pharmaceutical targets. Many drugs used today alter the GPCR signaling pathways,[8] notably calcitonin gene-related peptide receptor antagonists that are under investigation for the treatment of migraine.[10]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Aiyar N, Rand K, Elshourbagy NA, Zeng Z, Adamou JE, Bergsma DJ, Li Y (May 1996). "A cDNA encoding the calcitonin gene-related peptide type 1 receptor". J. Biol. Chem. 271 (19): 11325–9. doi:10.1074/jbc.271.19.11325. PMID 8626685. 
  4. ^ McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, Foord SM (May 1998). "RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor". Nature. 393 (6683): 333–9. doi:10.1038/30666. PMID 9620797. 
  5. ^ Foord SM, Marshall FH (May 1999). "RAMPs: accessory proteins for seven transmembrane domain receptors". Trends Pharmacol. Sci. 20 (5): 184–7. doi:10.1016/S0165-6147(99)01347-4. PMID 10354609. 
  6. ^ Kamitani S, Asakawa M, Shimekake Y, Kuwasako K, Nakahara K, Sakata T (April 1999). "The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells". FEBS Lett. 448 (1): 111–4. doi:10.1016/S0014-5793(99)00358-0. PMID 10217420. 
  7. ^ "Receptor properties". SenseLab Project: Membrane properties resource. Yale University. Retrieved 2008-09-28. 
  8. ^ a b PDB: 3N7S​; ter Haar E, Koth CM, Abdul-Manan N, Swenson L, Coll JT, Lippke JA, Lepre CA, Garcia-Guzman M, Moore JM (2010). "Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism". Structure. 18 (9): 1083–93. doi:10.1016/j.str.2010.05.014. PMID 20826335. 
  9. ^ Weston C, Winfield I, Harris M, Hodgson R, Shah A, Dowell SJ, Mobarec JC, Woodcock DA, Reynolds CA, Poyner DR, Watkins HA, Ladds G (August 2016). "Receptor activity modifying protein-directed G protein signaling specificity for the calcitonin gene-related peptide family of receptors receptor". The Journal of Biological Chemistry. 291: 21925–21944. doi:10.1074/jbc.M116.751362. PMC 5063977Freely accessible. PMID 27566546. 
  10. ^ LAUREN DUNN and PARMINDER DEO (February 24, 2017). "New Drugs May Stop Migraines Before They Start". NBC News. Retrieved February 24, 2017. 

Further reading[edit]

  • Born W, Muff R, Fischer JA (2002). "Functional interaction of G protein-coupled receptors of the adrenomedullin peptide family with accessory receptor-activity-modifying proteins (RAMP).". Microsc. Res. Tech. 57 (1): 14–22. doi:10.1002/jemt.10051. PMID 11921352. 
  • Yallampalli C, Chauhan M, Thota CS, et al. (2003). "Calcitonin gene-related peptide in pregnancy and its emerging receptor heterogeneity.". Trends Endocrinol. Metab. 13 (6): 263–9. doi:10.1016/s1043-2760(02)00563-5. PMID 12128288. 
  • Foord SM, Craig RK (1988). "Isolation and characterisation of a human calcitonin-gene-related-peptide receptor.". Eur. J. Biochem. 170 (1–2): 373–9. doi:10.1111/j.1432-1033.1987.tb13710.x. PMID 2826160. 
  • Skofitsch G, Jacobowitz DM (1986). "Autoradiographic distribution of 125I calcitonin gene-related peptide binding sites in the rat central nervous system.". Peptides. 6 (5): 975–86. doi:10.1016/0196-9781(85)90331-6. PMID 3001670. 
  • Flühmann B, Muff R, Hunziker W, et al. (1995). "A human orphan calcitonin receptor-like structure.". Biochem. Biophys. Res. Commun. 206 (1): 341–7. doi:10.1006/bbrc.1995.1047. PMID 7818539. 
  • Aiyar N, Rand K, Elshourbagy NA, et al. (1996). "A cDNA encoding the calcitonin gene-related peptide type 1 receptor.". J. Biol. Chem. 271 (19): 11325–9. doi:10.1074/jbc.271.19.11325. PMID 8626685. 
  • McLatchie LM, Fraser NJ, Main MJ, et al. (1998). "RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor.". Nature. 393 (6683): 333–9. doi:10.1038/30666. PMID 9620797. 
  • Sams A, Jansen-Olesen I (1999). "Expression of calcitonin receptor-like receptor and receptor-activity-modifying proteins in human cranial arteries.". Neurosci. Lett. 258 (1): 41–4. doi:10.1016/S0304-3940(98)00844-1. PMID 9876047. 
  • Kamitani S, Asakawa M, Shimekake Y, et al. (1999). "The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells.". FEBS Lett. 448 (1): 111–4. doi:10.1016/S0014-5793(99)00358-0. PMID 10217420. 
  • Aldecoa A, Gujer R, Fischer JA, Born W (2000). "Mammalian calcitonin receptor-like receptor/receptor activity modifying protein complexes define calcitonin gene-related peptide and adrenomedullin receptors in Drosophila Schneider 2 cells.". FEBS Lett. 471 (2–3): 156–60. doi:10.1016/S0014-5793(00)01387-9. PMID 10767413. 
  • Frayon S, Cueille C, Gnidéhou S, et al. (2000). "Dexamethasone increases RAMP1 and CRLR mRNA expressions in human vascular smooth muscle cells.". Biochem. Biophys. Res. Commun. 270 (3): 1063–7. doi:10.1006/bbrc.2000.2552. PMID 10772950. 
  • Kuwasako K, Shimekake Y, Masuda M, et al. (2000). "Visualization of the calcitonin receptor-like receptor and its receptor activity-modifying proteins during internalization and recycling.". J. Biol. Chem. 275 (38): 29602–9. doi:10.1074/jbc.M004534200. PMID 10882736. 
  • Evans BN, Rosenblatt MI, Mnayer LO, et al. (2000). "CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors.". J. Biol. Chem. 275 (40): 31438–43. doi:10.1074/jbc.M005604200. PMID 10903324. 
  • Hilairet S, Foord SM, Marshall FH, Bouvier M (2001). "Protein-protein interaction and not glycosylation determines the binding selectivity of heterodimers between the calcitonin receptor-like receptor and the receptor activity-modifying proteins.". J. Biol. Chem. 276 (31): 29575–81. doi:10.1074/jbc.M102722200. PMID 11387328. 
  • Kamitani S, Sakata T (2001). "Glycosylation of human CRLR at Asn123 is required for ligand binding and signaling.". Biochim. Biophys. Acta. 1539 (1–2): 131–9. doi:10.1016/S0167-4889(01)00100-8. PMID 11389975. 
  • Nikitenko LL, Brown NS, Smith DM, et al. (2001). "Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying proteins in the human uterus.". Mol. Hum. Reprod. 7 (7): 655–64. doi:10.1093/molehr/7.7.655. PMID 11420389. 
  • Hilairet S, Bélanger C, Bertrand J, et al. (2001). "Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin.". J. Biol. Chem. 276 (45): 42182–90. doi:10.1074/jbc.M107323200. PMID 11535606. 
  • Aiyar N, Disa J, Pullen M, Nambi P (2002). "Receptor activity modifying proteins interaction with human and porcine calcitonin receptor-like receptor (CRLR) in HEK-293 cells.". Mol. Cell. Biochem. 224 (1–2): 123–33. doi:10.1023/A:1011907328682. PMID 11693189. 
  • Hagner S, Haberberger RV, Overkamp D, et al. (2002). "Expression and distribution of calcitonin receptor-like receptor in human hairy skin.". Peptides. 23 (1): 109–16. doi:10.1016/S0196-9781(01)00586-1. PMID 11814625. 
  • Hill H, Pioszak A (2013). "Bacterial expression and purification of a heterodimeric adrenomedullin receptor extracellular domain complex using DsbC-assisted disulfide shuffling.". Protein Expr Purif. 88 (1): 107–13. doi:10.1016/j.pep.2012.11.019. PMC 3568255Freely accessible. PMID 23247088. 

External links[edit]